Exosomes derived from microRNA-512-5p-transfected bone mesenchymal stem cells inhibit glioblastoma progression by targeting JAG1.

In this study, we demonstrate that bone mesenchymal stem cell (BMSC)-derived exosomes alter tumor phenotypes by delivering miR-512-5p. miR-512-5p was downregulated in glioblastoma tissues and cells, and Jagged 1 (JAG1) was the target gene of miR-512-5p. We clarified the expression patterns of miR-512-5p and JAG1 along with their interactions in glioblastoma. Additionally, we observed that BMSC-derived exosomes could contain and transport miR-512-5p to glioblastoma cells in vitro. BMSC-derived exosomal miR-512-5p inhibited glioblastoma cell proliferation and induced cell cycle arrest by suppressing JAG1 expression. In vivo assays validated the in vitro findings, with BMSC-exosomal miR-512-5p inhibiting glioblastoma growth and prolonging survival in mice. These results suggest that BMSC-derived exosomes transport miR-512-5p into glioblastoma and slow its progression by targeting JAG1. This study reveals a new molecular mechanism for glioblastoma treatment and validates miRNA packaging into exosomes for glioblastoma cell communication.

MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women.

BACKGROUND: Stearoyl-coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. In this study, we examined whether this regulation by SCD1 is achieved by regulating the expression of related miRNAs. METHODS: SCD1 expression levels were observed in human bone-marrow mesenchymal stem cells (BM-MSCs) of patients with type 2 diabetes mellitus (T2DM), and the effect of SCD1 on osteogenesis was observed in human adipose-derived MSCs transfected with the SCD1 lentiviral system. We designed a bioinformatics prediction model to select important differentially expressed miRNAs, and established protein-protein interaction and miRNA-mRNA networks. miRNAs and mRNAs were extracted and their differential expression was detected. The SCD1-miRNA-mRNA network was validated. FINDINGS: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. The predictors in the nomogram were seven microRNAs, including hsa-miR-1908 and hsa-miR-203a. SCD1 inhibited the expression of CDKN1A and FOS, but promoted the expression of EXO1 and PLS1. miR-1908 was a regulator of EXO1 expression, and miR-203a was a regulator of FOS expression. INTERPRETATION: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR-203a/FOS and miR-1908/EXO1 regulatory pathways.

Differentiation of bMSCs on Biocompatible, Biodegradable, and Biomimetic Scaffolds for Largely Defected Tissue Repair.

Biocompatible, biodegradable, and biomimetic scaffolds in combination with stem cells are of great importance for tissue engineering, especially the repairing and regeneration of defected organs. As a case in point, esophageal diseases have become serious clinical problems because of the poor self-repairing ability of the organ. It is crucial to prepare artificial replacements with biological function for serious lesions of the esophagus. However, the pH value, mechanical strength, thickness, and other physical conditions are very different in different organs or different parts of the same organ, which pose high difficulty for successful tissue engineering. In this work, bone marrow mesenchymal stem cells (bMSCs) were isolated from rabbits and transfected with green fluorescent protein (GFP) to follow their capabilities of growth, stemness, and differentiation in ex vivo culture. These bMSCs were seeded on biocompatible, biodegradable, and biomimetic scaffolds to detect the tissue regenerative capability of the esophagus with multilayer hierarchical structure. According to the esophageal bilayer muscle architecture, we designed discontinuous and continuous microchannel patterned scaffolds with medical level polyurethane (PU) as the matrix to guide the inner-circular and outer-longitudinal muscle growth. The gap on the discontinuous walls not only helped cells to communicate with each other but also assisted cells to infiltrate through the gap and grew into the inner circular muscle. The graft of silk fibroin on the scaffold surface using the aminolysis and glutaraldehyde cross-linking method enhanced the substrate's hydrophilicity and biocompatibility. Mucosa-submucosa tissue of rabbit's esophagus was decellularized to obtain the extracellular matrix (ECM) and implanted in situ after recellularizing with bMSCs to repair the partially defected rabbits' esophagus. On the basis of both in vitro and in vivo results, we concluded that esophagus regeneration was promoted by the differentiation of bMSCs on the biocompatible, biodegradable, and biomimetic scaffolds, starting from tissue "niches", to repair the largely defected esophagus, which paves the way for tissue engineering and defected organ treatments.

Effect of intermittent tensile strain on proliferation and osteogenic differentiation of rat bone mesenchymal stem cells / 医用生物力学

Objective To investigate the effect of intermittent tensile strain on the proliferation and osteogenic differentiation of rBMSCs (rat bone mesenchymal stem cells). Methods Intermittent tensile strain was applied on rBMSCs in vitro by Flexcell 4 000 Tension System (10% elongation amplitude, 0.5 Hz, twice every day, 4 h every time), then effects of the strain after 1, 3, 5, 7 d on cell morphology, cell proliferation, and the relative expression of Cbfα1（core binding factor α1），ALP and collagen I mRNA as well as Cbfα1 protein were measured. Results Intermittent tensile strain slowed the proliferation of rBMSCs from the first day to the seventh day. The relative expression of ALP and collagen I mRNA increased by 3~6 times from the third day（P＜0.05）, meanwhile the expression of Cbfα1 mRNA and protein was up-regulated under the mechanical stimulation. Conclusions Mechanical stretch plays an important role in the proliferation and differentiation of rBMSC, and approprite intermittent tensile strain can slow the proliferation of rBMSC and promot its osteogenic differentiation.